The present invention relates to nutritional formulations for the support and therapy of individuals. More specifically, the present invention relates to nutritional compositions and methods of using same for preventing or treating renal disease and failure.
Acute renal failure ("ARF") refers to the clinical conditions associated with rapid, steadily increasing azotemia, with or without oliguria (&lt;500 mL/day). The cause of ARF can be grouped into three diagnostic categories: prerenal (inadequate renal perfusion); postrenal (obstruction); and renal. Merck Manual, 16th Edition, p. 1661 (1992).
The pathophysiology of ARF is complex and multifactorial. Current concepts suggest that ARF may result from the following mechanisms: (1) direct renal tubular injury; (2) renal ischemia; and (3) intra-tubular obstruction.
Direct as well as indirect toxic effects upon the kidney causes direct renal tubular injury. Examples of toxic antibiotics that can cause adverse reactions are aminoglycosides. Tubular injury may also arise following rhabdomyolysis. Free radicals, cytokines, and other toxins produced in response to a drug or injury mediate the indirect toxic effect upon the kidney.
Renal ischemia is one of the most common intrinsic renal causes of ARF. In general, renal ischemia refers to localized tissue hypoxia within kidneys that results from the obstruction of the inflow of blood or low blood oxygen levels. A number of conditions cause renal ischemia including diminished renal blood flow (e.g. shock states, amphotericin B), low cardiac output, and when the oxygen demand is greater than supply. In addition, renal artery vasoconstriction, increased renal vascular resistance, and abnormal tubuloglomerular feedback (TGF) may cause renal ischemia.
In addition to the previous two mechanisms, intra-tubular obstruction may also cause ARF. Intra-tubular obstruction may result from obstructions caused by such substances as cellular debris or protein.
Clinically, ARF results in diminished glomerular filtration and reduced secretion of metabolic waste products, water, and electrolytes. Fluid overload, electrolyte imbalances and the uremic syndrome result in organ dysfunction. Organ dysfunction may ultimately result in death.
Dialysis is commonly used to treat many of the metabolic disturbances of ARF. Dialysis is generally started as soon as possible after the diagnosis is established, since patients with advanced azotemia may deteriorate in an unpredictable manner. Unfortunately, however, morbidity from dialysis and persistence of renal failure are common.
Therefore, a need exists for a new mode of therapy for the prevention and treatment of ARF.